Long-Term Characterization of Firing Dynamics of Spontaneous Bursts in Cultured Neural Networks

Abstract

Extracellular action potentials were recorded from developing dissociated rat neocortical networks continuously for up to 49 days in vitro using planar multielectrode arrays. Spontaneous neuronal activity emerged toward the end of the first week in vitro and from then on exhibited periods of elevated firing rates, lasting for a few days up to weeks, which were largely uncorrelated among different recording sites. On a time scale of seconds to minutes, network activity typically displayed an ongoing repetition of distinctive firing patterns, including short episodes of synchronous firing at many sites (network bursts). Network bursts were highly variable in their individual spatio-temporal firing patterns but showed a remarkably stable underlying probabilistic structure (obtained by summing consecutive bursts) on a time scale of hours. On still longer time scales, network bursts evolved gradually, with a significant broadening (to about 2 s) in the third week in vitro, followed by a drastic shortening after about one month in vitro. Bursts at this age were characterized by highly synchronized onsets reaching peak firing levels within less than ca. 60 ms. This pattern persisted for the rest of the culture period. Throughout the recording period, active sites showed highly persistent temporal relationships within network bursts. These longitudinal recordings of network firing have, thus, brought to light a reproducible pattern of complex changes in spontaneous firing dynamics of bursts during the development of isolated cortical neurons into synaptically interconnected networks.

Measurement of saturation processes in glutamatergic and GABAergic synapse densities during long-term development of cultured rat cortical networks

“…5AB). In agreement with previous studies (Kamioka et al, 1996;van Pelt et al, 2004), we observed that the spontaneous spikes became synchronized bursts during the development of neuronal networks (Fig. 5B).…”

“…However, these previous studies focused mainly on early synaptic formation during early network construction. Network activity is known to show a mature pattern of synchronized bursting after random spontaneous activity in long-term culture (Kamioka et al, 1996;van Pelt et al, 2004;Chiappalone et al, 2006;Wagenaar et al, 2006). During this long-term development, however, how sufficient synaptic connections are established and how the density becomes saturated remain unclear.…”

Liquid state machines and cultured cortical networks: The separation property

“…Unlike simulated neural networks where the initial state and network configuration can be controlled, an LCN exhibits complicated spontaneous dynamics (Rolston et al, 2007;Segev et al, 2004;Wagenaar et al, 2006) whose activity patterns evolve over the course of development in vitro (van Pelt et al, 2004). These dynamics typically consist of episodes of increasing spontaneous asynchronous action potentials that culminate in a synchronous population burst of activity followed by a quiescent period.…”

Techniques and devices to restore cognition

“…Complex networks of neurons can be cultured in vitro and kept alive and physiologically active for years at a time. Multiple distinct spatiotemporal oscillatory patterns emerge spontaneously in these chronic neural cultures [160,161,166]. Populations of neurons attached to a multi-electrode array can be connected to tissue-engineered axons that are free to integrate with a host nerve stump upon transplantation [69,112].…”